ω-Aryl-13,14-didehydro-PGA compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 776,552, filed Mar. 7, 1977; which is a divisional application of Ser. No. 657,739, filed Feb. 13, 1976, issued as U.S. Pat. No. 4,029,681 on June 14, 1977.

The present invention relates to prostaglandin analogs, for which the essential material constituting disclosure therefor is incorporated by reference here from Ser. No. 657,739, filed Feb. 13, 1976, now issued as U.S. Pat. No. 4,029,681. 

I claim:
 1. A prostaglandin analog of the formula: ##STR1## wherein D is ##STR2## wherein Y₁ is --C.tbd.C--; wherein Z₆ is(1) cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --, (2) cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, (3) cis--CH₂ --CH═CH--(CH₂)_(g) --CH₂ --, (4) --(CH₂)₃ --(CH₂)_(g) --CH₂ --, or (5) --(CH₂)₃ --(CH₂)_(g) --CF₂ --, wherein g is one, 2, or 3; wherein Z₃ is oxa or methylene; wherein T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, and s is zero, one, 2, or 3, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl; wherein M₁ is ##STR3## wherein R₅ and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆ is methyl only when the other is hydrogen; wherein L₁ is ##STR4## or a mixture of ##STR5## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro and Z₃ is methylene; and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 2. A compound according to claim 1, wherein D is ##STR6##
 3. A compound according to claim 1, wherein D is ##STR7##
 4. A compound according to claim 3, wherein Z₃ is methylene.
 5. A compound according to claim 4, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 6. A compound according to claim 3, wherein Z₃ is oxa.
 7. A compound according to claim 6, wherein s is zero.
 8. A compound according to claim 6, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 9. A compound according to claim 8, wherein Z₆ is cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --.
 10. A compound according to claim 8, wherein Z₆ is cis--CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.
 11. A compound according to claim 8, wherein Z₆ is cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --.
 12. A compound according to claim 11, wherein M₁ is ##STR8##
 13. A compound according to claim 12, wherein g is one.
 14. A compound according to claim 13, wherein R₃, R₄, R₅, and R₆ are all hydrogen.
 15. 15-epi-16-Phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGA₂, methyl ester, a compound according to claim
 14. 16. A compound according to claim 11, wherein M₁ is ##STR9##
 17. A compound according to claim 16, wherein g is three.
 18. A compound according to claim 16, wherein g is one.
 19. A compound according to claim 18, wherein R₃ and R₄ are both hydrogen.
 20. A compound according to claim 19, wherein R₅ is methyl.
 21. 16-Phenoxy-17,18,19,20-tetranor-15-methyl-13,14-didehydro-PGA₂, a compound according to claim
 20. 22. 16-Phenoxy-17,18,19,20-tetranor-15-methyl-13,14-didehydro-PGA₂, methyl ester, a compound according to claim
 20. 23. A compound according to claim 19, wherein R₆ is methyl.
 24. 16-Phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGA₂, 15-methyl ether, a compound according to claim
 23. 25. 16-Phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGA₂, methyl ester, 15-methyl ether, a compound according to claim
 23. 26. A compound according to claim 19, wherein R₅ and R₆ are both hydrogen.
 27. 16-Phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGA₂, a compound according to claim
 26. 28. 16-Phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGA₂, methyl ester, a compound according to claim
 26. 29. A compound according to claim 18, wherein at least one of R₃ and R₄ is methyl.
 30. A compound according to claim 29, wherein R₃ and R₄ are both methyl.
 31. A compound according to claim 30, wherein R₅ is methyl.
 32. 16-Phenoxy-18,19,20-trinor-15,16-dimethyl-13,14-didehydro-PGA₂, methyl ester, a compound according to claim
 31. 33. A compound according to claim 30, wherein R₆ is methyl.
 34. 16-Phenoxy-18,19,20-trinor-16-methyl-13,14-didehydro-PGA₂, methyl ester, 15-methyl ester, a compound according to claim
 33. 35. A compound according to claim 30, wherein R₅ and R₆ are both hydrogen.
 36. 16-Phenoxy-18,19,20-trinor-16-methyl-13,14-didehydro-PGA₂, a compound according to claim
 35. 37. 16-Phenoxy-18,19,20-trinor-16-methyl-13,14-didehydro-PGA₂, methyl ester, a compound according to claim
 35. 38. A prostaglandin analog of the formula ##STR10## wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, or a pharmaceutically acceptable base;wherein one of R₂ and R₃ is hydroxy and the other is hydrogen; wherein R₄ is selected from the group consisting of hydrogen, methyl, and fluorine; and wherein T is selected from the group consisting of chloro, fluoro, trifluoromethyl or alkoxy of one to 3 carbon atoms. 